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Spontaneous firing frequency and typical PDS of CA1 pyramidal neurons in a 4-AP epilepsy model. (A) Representative typical traces of PDS. (B) Representative traces of spontaneous firing frequency and PDS from normal ACSF (nACSF), Control (CTL) after 10 min perfusion with 4-AP in low-Mg2 ACSF, NBP after 10 min perfusion with 4-AP + NBP in low-Mg2 ACSF, and washout after 15 min washout with 4-AP in low-Mg2 ACSF, where (a) presents activity with 25 μM NBP, (b) presents activity with 50 μM NBP, (C) presents activity with 100 μM NBP, (d) presents activity with 150 μM NBP, (e) presents activity with 200 μM NBP, (f) presents activity with 300 μM NBP, and (g) presents activity with 1000 μM NBP. Note that other concentrations of NBP were recorded (data not shown).
Source publication
Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epilept...
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It is known that top-down associative inputs terminate on distal apical dendrites in layer 1 while bottom-up sensory inputs terminate on perisomatic dendrites of layer 2/3 pyramidal neurons (L2/3 PyNs) in primary sensory cortex. Since studies on synaptic transmission in layer 1 are sparse, we investigated the basic properties and cholinergic modula...
Citations
... Han et al. found that NBP could reduce the level of the excitatory neurotransmitter glutamate in the brain of EP mice [12]. Yang et al. reported that NBP could reduce the amplitude of the miniature excitatory postsynaptic current and the EP-like electrical activity in EP rats [39]. In this experiment, NBP was used to intervene in PILO-induced EP rats. ...
Introduction:
The purpose of this study is to investigate whether Dl-3-n-Butylphthalide (NBP) has a neuroprotective effect on pilocarpine-induced epileptic (EP) rats through endoplasmic reticulum stress (ERS)-mediated apoptosis.
Material and methods:
The Sprague-Dawley rats were divided into four groups: control (CON), EP, EP + NBP 60 (NBP 60 mg/kg) and EP + NBP 120 (NBP 120 mg/kg) groups. After the successful establishment of the temporal lobe EP model using the lithium-pilocarpine, the rats were given NBP for 28 consecutive days in EP + NBP 60 and EP + NBP 120 groups. Then, the spontaneous recurrent seizure (SRS) latency, SRS frequency and seizure duration were observed in each group. In order to observe the abnormal discharge of rats, the intracranial electrodes were implanted to monitor the electroencephalogram. Nissl staining was used to observe the damage to the hippocampal CA1 neurons, TUNEL staining was employed to observe hippocampal neuronal apoptosis. Western blot was used to detect the expression of ERS and ERS-mediated apoptotic proteins.
Results:
NBP 60 and NBP 120 decreased SRS frequency (all p < 0.05), shortened seizure duration (all p < 0.05), and reduced the abnormal discharge of the brain. Nissl staining and TUNEL staining results show that NBP protected the hippocampal neurons from damage (all p < 0.05) and inhibited hippocampal neuronal apoptosis in EP rats (all p < 0.05). NBP 60 and NBP 120 could reduce ERS and ERS-mediated apoptotic protein expression in EP rats (all p < 0.05). In addition, the therapeutic effect of NBP on epilepsy in rats is dose-dependent. The SRS frequency of the EP + NBP 120 group was lower, and the seizure duration was shorter than in the EP + NBP 60 group (all p < 0.05), and there were more neurons in the EP + NBP 120 group than in the EP + NBP 60 group ( p < 0.05).
Conclusions:
NBP had a significant neuroprotective effect in EP rats. Large doses of NBP are more effective than low doses. The mechanism may be associated with the inhibition of ERS and ERS-mediated apoptosis.
... First, similar to how NBP improves the bradykinesia plus rigidity symptom of PD, NBP may exert neuroprotective effects through attenuation of neuroinflammatory responses. Furthermore, NBP was first purified from the seeds of Apium graveolens (Water celery) in 1978 at the Institute of Medicine of the Chinese Academy of Medical Sciences, inspired by a folk prescription for 'boiling of sailboat canvas and celery seeds together in water for the treatment of epilepsy', and in 1980, the compound was synthesized at the same institute for the first time (28). The pharmacological tests at that time demonstrated that NBP exhibited significant effects on the CNS, including anti-convulsant and sedative actions. ...
Currently available treatments for Parkinson's disease (PD) do not delay or prevent disease development and progression. DL-3-n-butylphthalide (NBP), isolated from Apium graveolens seeds, alleviates oxidative damage and mitochondrial dysfunction. It has been revealed to reduce the loss of dopamine neurons in pre-clinical PD models, and has been approved for the treatment of ischemic stroke patients. The purpose of the present study was to examine whether NBP has the capacity provide a benefit for PD patients and to slow disease progression. A randomized, controlled trial was performed between September 2014 and December 2016. Pairs of patients matched by age, gender and off-medication Unified PD Rating Scale motor subscale (UPDRS-III) scores, were randomly assigned to an NBP treatment group and a control group. All patients continued their originally prescribed medication regimen and those in the NBP group were administered NBP at 200 mg three times daily for 24 weeks. Primary outcome measures were changes in UPDRS-III, including tremor score and non-tremor score, the Pittsburgh sleep quality index (PSQI) and the PD 39-items questionnaire (PDQ) scores. Assessments were completed by blinded evaluators at baseline and 12, 24 and 48 weeks after randomization. All patients were monitored for adverse events (AEs). A total of 103 patients were enrolled in the present study. The NBP group exhibited significantly greater improvements in the non-tremor, PSQI and PDQ-39 scores than the control group, which generally exhibited no improvement. NBP-associated AEs were uncommon and primarily consisted of mild gastrointestinal symptoms. In conclusion, over the 6-month treatment period, NBP was safe and effective for improving the symptoms and impairing the progression of patients with PD (Trial registry number, ChiCTR1800018892).
Objective:
3-N-butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacological mechanisms including reconstructing microcirculation, protecting mitochondrial function, inhibiting oxidative stress, and inhibiting neuronal apoptosis and etc. Based on the complex multi-targets of pharmacological mechanisms of NBP, the clinical application of NBP is increasing and dried clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurological diseases and briefly summarize its application to non-neurological diseases. Moreover, recent progress in experimental models of NBP on animals was summarized.
Data sources:
Literature was collected from Pubmed until November 2018,using the search terms including "3-N-butylphthalide", "microcirculation", "mitochondria", "ischemic stroke", "Alzheimer's disease", "vascular dementia", "Parkinson's disease", "brain edema", "CO poisoning", "traumatic central nervous system injury", "autoimmune disease", "amyotrophic lateral sclerosis", "seizures", "diabetes", "diabetic cataract", and "atherosclerosis".
Study selection:
Literature was derived from English articles or articles that could be obtained from English abstracts. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors' files.
Results:
NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurological diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurological diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacological effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects.
Conclusions:
The varied pharmacological mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacological effects await further study.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
